Intestinal Neurogenin 3 directs differentiation of a bipotential secretory progenitor to endocrine cell rather than goblet cell fate

Abstract

Neurogenin 3 is essential for enteroendocrine cell development; however, it is unknown whether this transcription factor is sufficient to induce an endocrine program in the intestine or how it affects the development of other epithelial cells originating from common progenitors. In this study, the mouse villin promoter was used to drive Neurogenin 3 expression throughout the developing epithelium to measure the affect on cell fate. Although the general morphology of the intestine was unchanged, transgenic founder embryos displayed increased numbers of cells expressing the pan-endocrine marker chromogranin A. Accordingly, expression of several hormones and pro-endocrine transcription factors was increased in the transgenics suggesting that Neurogenin 3 stimulated a program of terminal enteroendocrine cell development. To test whether increased endocrine cell differentiation affected the development of other secretory cell lineages, we quantified goblet cells, the only other secretory cell formed in embryonic intestine. The Neurogenin 3-expressing transgenics had decreased numbers of goblet cells in correspondence to the increase in endocrine cells, with no change in the total secretory cell numbers. Thus, our data suggest that Neurogenin 3 can redirect the differentiation of bipotential secretory progenitors to endocrine rather than goblet cell fate.